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11/30/2017

The Aliens Within

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For many centuries humans have wondered what makes us look the way we look.  Why do people from different ethnicities still have a common recognizable body plan? What makes children look like their parents? These questions were all answered with the discovery and study of the molecule deoxyribonucleic acid, or DNA. Human DNA carries the blueprint to make a human being and keep it alive. It is because of DNA that all humans look more or less the same.

The way DNA works is that there are discrete sequences of this molecule called genes that carry the instructions to make proteins. The proteins thus made go on to make, organize, and maintain our bodies. But when scientists started sequencing the DNA molecules they found that the DNA in genes was the exception rather than the rule. Today we know that the 20,000 or so genes that human beings possess make up only 1.5% of the DNA in our bodies. The vast majority of our DNA (98.5%) is not organized into genes, and it’s not converted into proteins. What is it? The amazing answer seems to be that a good chunk of is not human!

About 8% of our DNA contains sequences that bear homology to a class of existing viruses called retroviruses (one example of a retrovirus is the AIDS virus, HIV). The viruses multiply by infecting an individual’s cells and inserting themselves into the cellular DNA. The cell’s machinery then makes more copies of the virus which go on to infect other cells and eventually get transmitted to other individuals. Once the virus has incorporated into the host’s cell DNA, it’s known as an endogenous virus. If the virus infects a sperm or an egg then it can be transmitted to all the cells of the offspring, and their offspring, and so on. Along the way in this process a virus may lose infectivity for several reasons and just become one more sequence of DNA.

This process seems to have happened multiple times during millions of years in the evolution of our ancestors. As a result today we have 5 times more viral DNA in our genome than we have genes coding for human proteins. However, as it turns out, this is merely the tip of the iceberg.

Endogenous viruses are just one class of elements that are called “transposable elements”. There are other classes of transposable elements that, like the viral elements, can transpose from one site in the DNA to another and get copied, but unlike the viral elements, these other transposable elements cannot leave the cell. There is uncertainty regarding the origin of these other transposable elements. Scientists have proposed that some of them evolved from viruses. Other transposable elements may have originated from endogenous molecules, but then acquired a parasitic independent life of their own. Be it as it may, all in all transposable elements comprise over 45% of our DNA, a whopping 30 times more DNA than that which is contained in the genes that code for human proteins! This calculation only takes into account transposable element sequences that can be recognized as such. It is very likely that the percentage is much higher, as many ancient transposable elements sequences in our genome have degraded due to mutation and other processes and are nowadays unrecognizable. It must also be pointed out that transposable elements are not only present in humans. All forms of life have transposable elements in their DNA, ranging from maize where transposable elements comprise 70% of the genome to bees where it is only 1%.

If DNA is indeed the blueprint to make and maintain a human being, what are we to make about this excess of alien DNA in our bodies? The answer can be found in evolution.

Transposable elements and organisms have coevolved through millions of years in an arms race where these elements sought to transpose and make more and more copies of themselves, and organisms sought to silence them lest they transpose to the middle of a vital gene compromising its function. Although transposable elements were very active in our evolutionary past, nowadays less than 0.05% of our transposable elements are still active, but their activity is associated with genetic diseases and even cancer.

However, this is half of the story. The other half is that organisms have figured out how to domesticate, modify, and co-opt transposable elements into important processes in our life cycles. For example, several genes of viral origin are used to make possible the development of the placenta. Without these genes we would not exist. Another example involves the adaptive immune system. To generate the diversity in antibodies necessary to fight off infection, immune cells employ a system derived from transposable elements. Without transposable elements forming part of our DNA we would not have a functioning adaptive immune system. We have also derived other benefits from transposable elements such as the expansion of our genomes with the creation of new genes and regulatory regions. In fact, transposable elements seem to have facilitated the very evolution of many species including ours.
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So these transposable elements that in the past were separate entities that pursued their own agendas within the bodies of our ancestors are now part of who we are: the aliens within are us!

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